Excessive alcohol intake often causes tissue injury, leading to severe medical disorders. It has long been recognized that alcohol abusers are susceptible to a wide range of infectious diseases, particularly pulmonary infection infections. Airway epithelia represent the first line of defense. They not only provide structural barriers and mechanical defense mechanisms, but also respond actively to bacterial challenge by secreting various cytokines to mobilize and modulate the host defens defense. Therefore, understanding alcohol effects on airway epithelial cells is critical to elucidate the cellular mechanisms of alcohol damage to airways. We hypothesize that alcohol exposure alters genomic and cytokine responses of airway epithelia to bacteri bacterial invasion and thus impairs the normal airway defense al mechanisms. The effects may render the epithelia susceptible to bacterial infection and injury. This R21 proposal is to use one unique air air-liquid interface airway epithelial culture model and two powerful gene and cytokine analysis approaches to investigate how alcohol affects airway epithelial cell gene expressions and cytokine productions. Three specific aims are proposed as follows. Specific Aim 1: to determine the effect of alcohol on cytokine and c chemokine production by human airway epithelial cells hemokine using the cytokine multiplex array approach;Specific Aim 2: to determine the effect of alcohol on gene expression profile of human airway epithelial cells by GeneChip analysis;Specific Aim 3: to study the effects of alcohol on airway epithelial viability and integrity. Through completion of the specific aims, we expect to gain knowledge on how alcohol leads to human airway damage at the molecular and cellular levels, which may predispose patients to al alcohol cohol-associated pulmonary infections and injury. This research may provide information for the development of potential therapeutics to control or modify outcomes of alcohol abuse.